Skin lightening agents, compositions and methods

ABSTRACT

Cosmetic compositions and methods of skin lightening using compounds of formula I as skin lightening agents: 
                 
 
Wherein X represents Carbon, Nitrogen, Sulfur or Oxygen;
         each A 1  and/or A 2  independently is =H or COR, CO 2 R, CONHR having the following formula A: 
                 
 
where R=C 1 -C 18  saturated or unsaturated, linear or branched, hydrocarbon; and
   each Y 1  and/or Y 2  independently is C 1 -C 18  saturated or unsaturated hydrocarbon or OZ, where Z=H or COR 1 , CO 2 R 1 , CONHR 1  of formula B: 
                 
 
and where R 1 =C 1 -C 18  saturated or unsaturated, linear or branched, hydrocarbon.

FIELD OF THE INVENTION

The invention relates to cosmetic methods of using 4-substitutedresorcinol derivative compounds and cosmetic compositions includingsame, and more specifically, 1,3-dithiane resorcinol derivatives, asskin lightening agents.

BACKGROUND OF THE INVENTION

Many people are concerned with the degree of pigmentation of their skin.For example, people with age spots or freckles may wish such pigmentedspots to be less pronounced. Others may wish to reduce the skindarkening caused by exposure to sunlight or to lighten their naturalskin color. To meet this need, many attempts have been made to developproducts that reduce the pigment production in the melanocytes. However,the substances identified thus far tend to have either low efficacy orundesirable side effects, such as, for example, toxicity or skinirritation. Therefore, there is a continuing need for new skinlightening agents, with improved overall effectiveness.

Resorcinol derivatives have cosmetic skin and hair benefits. Certainresorcinol derivatives, particularly 4-substituted resorcinolderivatives, are useful in cosmetic compositions for skin lighteningbenefits. Resorcinol derivatives are described in many publications,including Hu et al., U.S. Pat. No. 6,132,740; Collington et al., PCTPatent Application WO 00/56702; Bradley et al., European PatentApplication EP 1 134 207; Shinomiya et al., U.S. Pat. No. 5,880,314;LaGrange et al., U.S. Pat. No. 5,468,472; Hiroaki et al., JapanesePatent Application JP11-255638 A2; Torihara et al., U.S. Pat. No.4,959,393; and Japanese published patent applications JP 2001-010925 andJP2000-327557. Resorcinol derivatives are known compounds and can bereadily obtained by various means, including by a method wherein asaturated carboxylic acid and resorcinol are condensed in the presenceof zinc chloride and the resultant condensate is reduced with zincamalgam/hydrochloric acid (Lille, et al., Tr. Nauch-Issled. Inst.Slantsev 1969, No. 18:127-134), or by a method wherein resorcinol and acorresponding alkyl alcohol are reacted in the presence of an aluminacatalyst at a high temperature of from 200 to 400° C. (British PatentNo. 1,581,428). Some of these compounds can be irritating to the skin.

Applicants have now discovered that the use of 1,3-dithiane resorcinolsdeliver skin lightening benefits. The general chemical formulas andstructures of these compounds are discussed in more detail herein below.The 1,3-dithiane resorcinos have been found to be effective and possiblyless irritating to the skin and have not been used for lightening skin.

SUMMARY OF THE INVENTION

The use of compounds of the general formula I, and compositionsincluding same, delivers skin lightening benefits with potential reducedirritation. The present invention provides a cosmetic composition andmethod of skin lightening using in addition to a cosmetically acceptablevehicle, about 0.000001 to about 50% of a compound of formula I,

Where:

-   X=Carbon, Nitrogen, Sulfur or Oxygen; and-   each A₁ and/or A₂ independently is =H or COR (acyl group), CO₂R,    CONHR having the following formula A:    where R=C₁-C₁₈ saturated or unsaturated, linear or branched,    hydrocarbon; and-   each Y₁ and/or Y₂ independently is C₁-C₁₈ saturated or unsaturated    hydrocarbon or OZ, where Z=H or COR¹, CO₂R¹, CONHR¹ of formula B:    and where R¹=C₁-C₁₈ saturated or unsaturated, linear or branched,    hydrocarbon.

In a preferred embodiment, each or both A₁ and/or A₂ represents H andeach Y₁ and/or Y₂ represents H. In a more preferred embodiment, both A₁and A₂ represent H, and both Y₁ and Y₂ represent H, so that the compoundis of formula II as follows (with X defined as above with reference toformula I):

Optionally, the hydroxy groups may be further substituted by methodsknown in the art. For example, the one or both hydroxy groups may beesterified with any or a combination of the following acids: ferulicacid, vanillic acid, sebacic acid, azaleic acid, benzoic acid, caffeicacid, coumaric acid, salicylic acid, cysteine, cystine, lactic acid, andglycolic acid.

Further skin benefit agents may be included in the compositions usefulfor the inventive method. Organic and inorganic sunscreens, as well asperfumes, may also be included.

The inventive compositions and methods have effective skin lighteningproperties, may be less irritating to the skin, and are cost-effective.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, the term “cosmetic composition” is intended to describecompositions for topical application to human skin.

The term “skin” as used herein includes the skin on the face, neck,chest, back, arms, axilla, hands, legs, and scalp.

Except in the examples, or where otherwise explicitly indicated, allnumbers in this description indicating amounts of material or conditionsof reaction, physical properties of materials and/or use are to beunderstood as modified by the word “about”. All amounts are by weight ofthe composition, unless otherwise specified.

It should be noted that in specifying any range of concentration, anyparticular upper concentration can be associated with any particularlower concentration.

For the avoidance of doubt the word “comprising” is intended to meanincluding but not necessarily consisting of or composed of. In otherwords the listed steps or options need not be exhaustive.

Skin Lightening Agents

The invention is concerned with the use of compounds of general formulaI, shown below, and compositions including same, as skin lighteningagents. A particular advantage of the inventive compositions and methodsis that compounds of general formula I can be less irritating to theskin than other, known, skin lightening compounds. The present inventionprovides a cosmetic composition and method of skin lightening using inaddition to a cosmetically acceptable vehicle, about 0.000001 to about50% of a compound of formula I,

Where:

-   X=Carbon, Nitrogen, Sulfur or Oxygen; and-   each A₁ and/or A₂ independently is =H or COR (acyl group), CO₂R,    CONHR, the latter three having the following formula A,    respectively:    where R=C₁-C₁₈ saturated or unsaturated, linear or branched,    hydrocarbon; and each Y₁ and/or Y₂ independently is C₁-C₁₈ saturated    or unsaturated hydrocarbon or OZ, where Z=H or COR¹, CO₂R¹, CONHR¹    of formula B:    and where R¹=C₁-C₁₈ saturated or unsaturated, linear or branched,    hydrocarbon.

In a preferred embodiment, each or both A₁ and/or A₂ represents OH andeach or both Y₁ and/or Y₂ represents H. In a more preferred embodiment,both A₁ and A₂ represent OH and both Y₁ and Y₂ represent H, so that thecompound is of formula II as follows (with X defined as above withreference to formula I):

In the compound of general formula II, optionally, the hydroxy groups(the hydrogen on one or both of the OH-groups) may be furthersubstituted by methods known in the art. For example, one or bothhydroxy groups may be esterified with any or a combination of thefollowing acids: ferulic acid, vanillic acid, sebacic acid, azaleicacid, benzoic acid, caffeic acid, coumaric acid, salicylic acid,cysteine, cystine, lactic acid, and glycolic acid.

Procedure for Making 1,3-dithiane Resorcinol

In a most preferred embodiment, both A₁ and A₂ represent H, both Y₁ andY₂ represent H, and X represents Carbon. This most preferred embodiment,referred to herein as 1,3-dithiane resorcinol, may be prepared byreaction of 2,4-dihydroxy benzaldehyde and 1,3-Dimercaptopropane (Bothstarting materials are available from Yick-Vic Chemicals &Pharmaceuticals (HK) Ltd/Hong Kong), denoted by the following formulaIII and catalyzed by an acid catalyst. Suitable catalysts include butare not limited to methane sulfonic acid, p-toluene sulfonic acid, H₂SO₄(sulfuric acid), HCl (hydrochloric acid) and acidic resins.

A three necked flask equipped with a Dean-Stark apparatus, an additionalfunnel and a condenser is charged with 2,4-dihydroxy benzaldehyde (1equ.). To this was added toluene (500 ml) and a catalytic amount ofp-toluene sulfonic acid. The mixture was heated at 120 C. One equivalentof 1,3-dithiopropane in toluene (100 ml) was added dropwise to themixture. The mixture was stirred at reflux up to 12 hrs. The solvent wasremoved on a rotavap and the expected product was isolated. Thestructure of the dithiane was confirmed using Mass spectroscopy, NMR andIR.

The inventive compositions and methods have effective skin lighteningproperties, may be less irritating to the skin than other skinlightening actives, and are relatively easy to manufacture andcost-effective.

The compositions generally contain about 0.000001 to about 50% ofcompounds of general formula I, II, and/or. Compounds of general formulaII are preferred, and compounds of formula III are most preferred. Theamount of the inventive compound is preferably in the range of about0.00001% to about 10%, more preferably about 0.001 to about 7%, mostpreferably from 0.01 to about 5%, of the total amount of cosmeticcomposition. Further skin benefit agents may be included in thecompositions useful for the inventive method. Organic and inorganicsunscreens, as well as fragrances, may also be included.

Optional Skin Benefit Agents

Preferred cosmetic compositions are those suitable for the applicationto human skin according to the method of the present invention, whichoptionally, but preferably, include a skin benefit agent in addition toa compound of general formula I.

Suitable additional skin benefit agents include anti-aging,wrinkle-reducing, skin whitening, anti-acne, and sebum reduction agents.Examples of these include alpha-hydroxy acids, beta-hydroxy acids,polyhydroxy acids, hydroquinone, t-butyl hydroquinone, niacinamide,Vitamic C derivatives, dioic acids (e.g., malonic acid, sebacic acid),linoleic acid, retinoids, and resorcinol derivatives other than compoundof general formula I of the present invention.

Cosmetically Acceptable Carrier

The cosmetically acceptable vehicle may act as a dilutant, dispersant orcarrier for the skin benefit ingredients in the composition, so as tofacilitate their distribution when the composition is applied to theskin.

The vehicle may be aqueous, anhydrous or an emulsion. Preferably, thecompositions are aqueous or an emulsion, especially water-in-oil oroil-in-water emulsion, preferably oil in water emulsion. Water whenpresent will be in amounts which may range from 5 to 99%, preferablyfrom 20 to 70%, optimally between 40 and 70% by weight.

Besides water, relatively volatile solvents may also serve as carrierswithin compositions of the present invention. Most preferred aremonohydric C₁-C₃ alkanols. These include ethyl alcohol, methyl alcoholand isopropyl alcohol. The amount of monohydric alkanol may range from 1to 70%, preferably from 10 to 50%, optimally between 15 to 40% byweight.

Emollient materials may also serve as cosmetically acceptable carriers.

These may be in the form of silicone oils and synthetic esters. Amountsof the emollients may range anywhere from 0.1 to 50%, preferably between1 and 20% by weight.

Silicone oils may be divided into the volatile and non-volatile variety.The term “volatile” as used herein refers to those materials which havea measurable vapor pressure at ambient temperature. Volatile siliconeoils are preferably chosen from cyclic or linear polydimethylsiloxanescontaining from 3 to 9, preferably from 4 to 5, silicon atoms. Linearvolatile silicone materials generally have viscosities less than about 5centistokes at 25° C. while cyclic materials typically have viscositiesof less than about 10 centistokes. Nonvolatile silicone oils useful asan emollient material include polyalkyl siloxanes, polyalkylarylsiloxanes and polyether siloxane copolymers. The essentiallynon-volatile polyalkyl siloxanes useful herein include, for example,polydimethyl siloxanes with viscosities of from about 5 to about 25million centistokes at 25° C. Among the preferred non-volatileemollients useful in the present compositions are the polydimethylsiloxanes having viscosities from about 10 to about 400 centistokes at25° C.

Among the ester emollients are:

-   -   (1) Alkenyl or alkyl esters of fatty acids having 10 to 20        carbon atoms. Examples thereof include isoarachidyl        neopentanoate, isononyl isonanonoate, oleyl myristate, oleyl        stearate, and oleyl oleate.    -   (2) Ether-esters such as fatty acid esters of ethoxylated fatty        alcohols.    -   (3) Polyhydric alcohol esters. Ethylene glycol mono and di-fatty        acid esters, diethylene glycol mono- and di-fatty acid esters,        polyethylene glycol (200-6000) mono- and di-fatty acid esters,        propylene glycol mono- and di-fatty acid esters, polypropylene        glycol 2000 monooleate, polypropylene glycol 2000 monostearate,        ethoxylated propylene glycol monostearate, glyceryl mono- and        di-fatty acid esters, polyglycerol poly-fatty esters,        ethoxylated glyceryl monostearate, 1,3-butylene glycol        monostearate, 1,3-butylene glycol distearate, polyoxyethylene        polyol fatty acid ester, sorbitan fatty acid esters, and        polyoxyethylene sorbitan fatty acid esters are satisfactory        polyhydric alcohol esters.    -   (4) Wax esters such as beeswax, spermaceti, myristyl myristate,        stearyl stearate and arachidyl behenate.    -   (5) Sterol esters, of which cholesterol fatty acid esters are        examples.

Fatty acids having from 10 to 30 carbon atoms may also be included ascosmetically acceptable carriers for compositions of this invention.Illustrative of this category are pelargonic, lauric, myristic,palmitic, stearic, isostearic, hydroxystearic, oleic, linoleic,ricinoleic, arachidic, behenic and erucic acids.

Humectants of the polyhydric alcohol-type may also be employed ascosmetically acceptable carriers in compositions of this invention. Thehumectant aids in increasing the effectiveness of the emollient, reducesscaling, stimulates removal of built-up scale and improves skin feel.Typical polyhydric alcohols include glycerol, polyalkylene glycols andmore preferably alkylene polyols and their derivatives, includingpropylene glycol, dipropylene glycol, polypropylene glycol, polyethyleneglycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol,hexylene glycol, 1,3-butylene glycol, 1,2,6-hexanetriol, ethoxylatedglycerol, propoxylated glycerol and mixtures thereof. For best resultsthe humectant is preferably propylene glycol or sodium hyaluronate. Theamount of humectant may range anywhere from 0.5 to 30%, preferablybetween 1 and 15% by weight of the composition.

Thickeners may also be utilized as part of the cosmetically acceptablecarrier of compositions according to the present invention. Typicalthickeners include crosslinked acrylates (e.g. Carbopol 982),hydrophobically-modified acrylates (e.g. Carbopol 1382), cellulosicderivatives and natural gums. Among useful cellulosic derivatives aresodium carboxymethylcellulose, hydroxypropyl methylcellulose,hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose andhydroxymethyl cellulose. Natural gums suitable for the present inventioninclude guar, xanthan, sclerotium, carrageenan, pectin and combinationsof these gums. Amounts of the thickener may range from 0.0001 to 5%,usually from 0.001 to 1%, optimally from 0.01 to 0.5% by weight.

Collectively the water, solvents, silicones, esters, fatty acids,humectants and/or thickeners will constitute the cosmetically acceptablecarrier in amounts from 1 to 99.9%, preferably from 80 to 99% by weight.

An oil or oily material may be present, together with an emulsifier toprovide either a water-in-oil emulsion or an oil-in-water emulsion,depending largely on the average hydrophilic-lipophilic balance (HLB) ofthe emulsifier employed.

Surfactants may also be present in cosmetic compositions of the presentinvention. Total concentration of the surfactant will range from 0.1 to40%, preferably from 1 to 20%, optimally from 1 to 5% by weight of thecomposition. The surfactant may be selected from the group consisting ofanionic, nonionic, cationic and amphoteric actives. Particularlypreferred nonionic surfactants are those with a C₁₀-C₂₀ fatty alcohol oracid hydrophobe condensed with from 2 to 100 moles of ethylene oxide orpropylene oxide per mole of hydrophobe; C₂-C₁₀ alkyl phenols condensedwith from 2 to 20 moles of alkylene oxide; mono- and di-fatty acidesters of ethylene glycol; fatty acid monoglyceride; sorbitan, mono- anddi-C₈-C₂₀ fatty acids; block copolymers (ethylene oxide/propyleneoxide); and polyoxyethylene sorbitan as well as combinations thereof.Alkyl polyglycosides and saccharide fatty amides (e.g. methylgluconamides) are also suitable nonionic surfactants.

Preferred anionic surfactants include soap, alkyl ether sulfate andsulfonates, alkyl sulfates and sulfonates, alkylbenzene sulfonates,alkyl and dialkyl sulfosuccinates, C₈-C₂₀ acyl isethionates, acylglutamates, C₈-C₂₀ alkyl ether phosphates and combinations thereof.

Optional Components

In the cosmetic compositions of the invention, there may be addedvarious medically effective ingredients, such as allantoin, a placentaextract; other thickeners, plasticizers; calamine; pigments;antioxidants; and chelating agents; as well as additional sunscreenssuch organic sunscreens, typical of which are PARSOL 1789 and PARSOLMCX.

Other adjunct minor components may also be incorporated into thecosmetic compositions. These ingredients may include coloring agents,opacifiers, and perfumes. Amounts of these other adjunct minorcomponents may range anywhere from 0.001% up to 20% by weight of thecomposition.

Sunscreens

For use as sunscreen, metal oxides may be used alone or in mixtureand/or in combination with organic sunscreens. Examples of organicsunscreens include but are not limited those set forth in the tablebelow:

TABLE 1 Typical Organic Sunscreens CTFA Name Trade Name SupplierBenzophenone-3 UVINUL M-40 BASF Chemical Co. Benzophenone-4 UVINUL MS-40BASF Chemical Co. Benzophenone-8 SPECRA-SORB UV-24 American CyanamideDEA Methoxycinnamate BERNEL HYDRO Bernel Chemical Ethyldihydroxypropyl-PABA AMERSCREEN P Amerchol Corp. Glyceryl PABA NIPAG.M.P.A. Nipa Labs. Homosalate KEMESTER HMS Hunko Chemical Methylanthranilate SUNAROME UVA Felton Worldwide Octocrylene UVINUL N-539 BASFChemical Co. Octyl dimethyl PABA AMERSCOL Amerchol Corp. Octylmethoxycinnamate PARSOL MCX Bernel Chemical Octyl salicylate SUNAROMEWMO Felton Worldwide PABA PABA National Starch2-Phenylbenzimidazole-5-sulphonic acid EUSOLEX 232 EM Industries TEAsalicylate SUNAROME W Felton Worldwide 3-(4-methylbenzylidene)-camphorEUSOLEX 6300 EM Industries Benzophenone-1 UVINUL 400 BASF Chemical Co.Benzophenone-2 UVINUL D-50 BASF Chemical Co. Benzophenone-6 UVINUL D-49BASF Chemical Co. Benzophenone-12 UVINUL 408 BASF Chemical Co.4-Isopropyl dibenzoyl methane EUSOLEX 8020 EM Industries Butyl methoxydibenzoyl methane PARSOL 1789 Givaudan Corp. Etocrylene UVINUL N-35 BASFChemical Co.

The amount of the organic sunscreens in the cosmetic composition ispreferably in the range of about 0.1 wt % to about 10 wt %, morepreferably about 1 wt % to 5 wt %.

Preferred organic sunscreens are PARSOL MCX and Parsol 1789, due totheir effectiveness and commercial availability.

Perfumes

Perfumes are fragrance compositions that are mixtures of componentsproviding, usually, a pleasing sense of smell. Terpenes and terpenederivatives are often an important component of fragrances. Fragranceterpenes and derivatives are described in Bauer, K., et al., CommonFragrance and Flavor Materials, VCH Publishers (1990).

Terpenes and derivatives that may preferably be incorporated in theinventive cosmetic compositions are divided into three classes,including acyclic terpenoids, cyclic terpenoids, and cycloaliphaticcompounds that are structurally related to terpenoids.

Terpene derivatives within each of the three classes include alcohols,ethers, aldehydes, acetals, acids, ketones, esters, and terpenecompounds that contain heteroatoms such as nitrogen or sulfur.

Examples of terpenes and derivative that may be incorporated in thecosmetic compositions of the present invention are set forth in thetables below:

TABLE 2 Acyclic Terpenes and Derivatives HYDROCARBONS Myrcene Ocimenebeta-Farnesene ALCOHOLS Dihydromyrcenol (2,6-dimethyl-7-octen-2-ol)Geraniol (3,7-dimethyl-trans-2,6-octadien-1-ol) Nerol(3,7-dimethyl-cis-2,6-octadien-1-ol) Linalool(3,7-dimethyl-1,6-octadien-3-ol) Myrcenol(2-methyl-6-methylene-7-octen-2-ol) Lavandulol Citronellol(3,7-dimethyl-6-octen-1-ol) Trans-trans-Farnesol(3,7,11-trimethyl-2,6,10-dodecatrien-1-ol) Trans-Nerolidol(3,7,11-trimethyl-1,6,10-dodecatrien-3-ol) ALDEHYDES AND ACETALS Citral(3,7-dimethyl-2,6-octadien-1-al) Citral diethyl acetal(3,7-dimethyl-2,6-octadien-1- al diethyl acetal) Citronellal(3,7-dimethyl-6-octen-1-al) Citronellyloxyacetaldehyde2,6,10-Trimethyl-9-undecenal KETONES Tagetone Solanone Geranylacetone(6,10-dimethyl-5,9-undecadien-2-one) ACIDS AND ESTERS Cis-Geranic acidCitronellic acid Geranyl Esters, including Geranyl formate, Geranylacetate, Geranyl propionate, Geranyl isobutyrate, Geranyl isovalerateNeryl Esters, including Neryl acetate Linalyl Esters, including Lynalylformate, Linalyl acetate, Linalyl propionate, Linalyl butyrate, Linalylisobutyrate, Lavandulyl Esters, including Lavendulyl acetate CitronellylEsters, including Citronellyl formate, Citronellyl acetate, Citronellylpropionate, Citronellyl isobutyrate, Citronellyl isovalerate,Citronellyl tiglate NITROGEN CONTAINING UNSATURATED TERPENE DERIVATIVESCis-Geranic acid nitrile Citronellic acid nitrile

TABLE 3 Cyclic Terpenes and Derivatives HYDROCARBONS Limonene(1,8-p-menthadiene) Alpha-Terpinene Gamma-Terpinene (1,4-p-menthadiene)Terpinolene Alpha-Phellandrene (1,5-p-menthadiene) Beta-PhellandreneAlpha-Pinene (2-pinene) Beta-Pinene (2(10)-pinene) Camphene 3-CareneCaryophyllene (+)-Valencene Thujopsene Alpha-Cedrene Beta-CedreneLongifolene ALCOHOLS AND ETHERS (+)-Neoiso-isopulegol Isopulegol(8-p-menten-3-ol) Alpha-Terpineol (1-p-menten-8-ol) Beta-TerpineolGamma-Terpineol Delta-Terpineol 1-Terpinen-4-ol (1-p-menten-4-ol)ALDEHYDES AND KETONES Carvone (1,8-p-mantadien-6-one) Alpha-Ionone(C₁₃H₂₀O) Beta-Ionone (C₁₃H₂₀O) Gamma-Ionone (C₁₃H₂₀O) Irone, alpha-,(C₁₄H₂₂O) beta-, gamma- n-Methylionone, (C₁₄H₂₂O) alpha-, beta-, gamma-Isomethylionone, (C₁₄H₂₂O) alpha-, beta-, gamma- Allylionone (C₁₆H₂₄O)Pseudoionone n-Methylpseudoionone Isomethylpseudoionone Damascones1-(2,6,6-trimethylcyclohexenyl)- 2-buten-1-ones Includingbeta-Damascenone 1-(2,6,6-trimethyl- 1,3-cyclohadienyl)- 2-buten-1-oneNootkatone 5,6-dimethyl-8- isopropenylbicyclo[4.4.0]-1- decen-3-oneCedryl methyl ketone (C₁₇H₂₆O) ESTERS Alpha-Terpinyl acetate(1-p-menthen-8-yl acetate) Nopyl acetate(−)-2-(6,6-dimethylbicyclo[3.1.1]hept- 2-en-2-yl)ethyl acetate Khusymilacetate

TABLE 4 Cycloaliphatic Compounds Structurally Related to TerpenesALCOHOLS 5-(2,2,3-Trimethyl-3-cyclopenten-1-yl)-3-methylpentan-2-olALDEHYDES 2,4-Dimethyl-3-cyclohexene carboxaldehyde4-(4-Methyl-3-penten-1-yl)-3-cyclohexene carboxaldehyde4-(4-Hydroxy-4-methypentyl)-3-cyclohexene carboxaldehyde KETONESCivetone Dihydrojasmone (3-methyl-2-pentyl-2-cyclopenten-1-one)Cis-Jasmone 3-methyl-2-(2-cis-penten-1-yl)-2-cyclopenten-1- one5-Cyclohexadecen-1-one2,3,8,8-Tetramethyl-1,2,3,4,5,6,7,8-octahydro-2-napthalenyl methylketone 3-methyl-2-cyclopenten-2-ol-1-one ESTERS4,7-Methano-3a,4,5,6,7,7a-hexahydro-5-(or 6)-indenyl acetate Allyl3-cyclohexylpropionate Methyl dihydrojasmonate methyl(3-oxo-pentylcyclopentyl)acetate

Preferably, the amount of terpenes and derivatives in the cosmeticcomposition is in the range of about 0.000001% to about 10%, morepreferably about 0.00001% to about 5 wt %, most preferably about 0.0001%to about 2%.

Use of the Composition

The method according to the invention is intended primarily as using apersonal care product for topical application to human skin.

In use, a small quantity of the composition, for example from 1 to 5 ml,is applied to exposed areas of the skin, from a suitable container orapplicator and, if necessary, it is then spread over and/or rubbed intothe skin using the hand or fingers or a suitable device.

Product Form and Packaging

The cosmetic composition useful for the method of the invention can beformulated as a lotion having a viscosity of from 4,000 to 10,000 mPas,a fluid cream having a viscosity of from 10,000 to 20,000 mPas or acream having a viscosity of from 20,000 to 100,000 mPas, or above. Thecomposition can be packaged in a suitable container to suit itsviscosity and intended use by the consumer. For example, a lotion orfluid cream can be packaged in a bottle or a roll-ball applicator or apropellant-driven aerosol device or a container fitted with a pumpsuitable for finger operation. When the composition is a cream, it cansimply be stored in a non-deformable bottle or squeeze container, suchas a tube or a lidded jar. When the composition is a solid or semi-solidstick, it may be packaged in a suitable container for manually ormechanically pushing out or extruding the composition.

The invention accordingly also-provides a closed container containing acosmetically acceptable composition as herein defined.

The following examples are by way of example, not by way of limitation,of the principles of the present invention, to illustrate the best modeof carrying out the invention.

EXAMPLE 1

The following compound, referred to herein as di-thiane resorcinol,prepared by the method described above, was used throughout the examplesthat follow:

EXAMPLE 2

Cosmetic compositions within the scope of the invention were prepared.

A base formulation shown in Table 3, below, was made by heating phase Aingredients to 70 to 85° C. with stirring. Phase B ingredients wereheated in a separate container to 70 to 85° C. with stirring. Then,phase A was added into phase B while both phases were kept at 70 to 85°C. The mixture was stirred for at least 15 minutes at 70 to 85° C., thencooled.

A base formulation is shown in the table below.

TABLE 5 a b Ingredients % wt. % wt. Phase Isostearyl Palmitate 6.00 6.00A C12-C15 Alkyl Octanoate 3.00 3.00 A PEG-100 Stearate 2.00 2.00 AGlyceryl Hydroxystearate 1.50 1.50 A Stearyl Alcohol 1.50 1.50 A Stearicacid 3.00 4.00 A TEA, 99% 1.20 1.20 B Dimethicone 1.00 1.00 A SorbitanMonostearate 1.00 1.00 A Magnesium Aluminum Silicate 0.60 0.60 B VitaminE acetate 0.10 0.10 A Cholesterol 0.50 0.50 A Simethicone 0.01 0.01 BXanthan gum 0.20 0.20 B Hydroxyethylcellulose 0.50 0.50 B Propylparaben0.10 0.10 B Disodium EDTA 0.05 0.05 B Butylated hydroxytolene 0.05 0.05B Di-Thiane Resorcinol) 0.05 2.00 B Niacinamide 1.00 1.00 B Metal oxide2.50 5.00 B Methylparaben 0.15 0.15 B Water BAL* BAL* B Total 100.00 100.00  B *BAL means Balance.

EXAMPLE 3

Additional cosmetic compositions within the scope of the invention wereprepared.

TABLE 6 Wt % Phase water, DI BALANCE A disodium EDTA 0.05 A magnesiumaluminum silicate 0.6 A methyl paraben 0.15 A simethicone 0.01 Abutylene glycol 1,3 3.0 A hydroxyethylcellulose 0.5 A glycerine, USP 2.0A xanthan gum 0.2 A triethanolamine 1.2 B stearic acid 3.0 B propylparaben NF 0.1 B glyceryl hydroxystearate 1.5 B stearyl alcohol 1.5 Bisostearyl palmitate 6.0 B C12-15 alcohols octanoate 3.0 B dimethicone1.0 B cholesterol NF 0.5 B sorbitan stearate 1.0 B Micronized titaniumdioxide 5.0 C tocopheryl acetate 0.1 B PEG-100 stearate 2.0 B sodiumstearoyl lactylate 0.5 B hydroxycaprylic acid 0.1 C Di-Thiane Resorcinol10.0 C PARSOL MCX 2.4 C alpha-bisabolol 0.2 C

The composition of Example 3, was prepared as follows:

-   -   1. Heat Phase A to 80° C.    -   2. Heat Phase B to 75° C. in a separate container    -   3. Add B to A and mix with heat off for 30 min.    -   4. At 50° C. add Phase C and mix for 10 min.

EXAMPLES 4-11

A set of additional compositions useful in the methods of the presentinvention were prepared within the scope of the present invention andare listed in the table below.

TABLE 7 Examples (wt. %) 4 acid soap Ingredients Phase base 5 6 7 8 9 1011 Stearic acid A 17.9 17.9 17.9 17.9 17.9 17.9 17.9 17.9 Sodiumcetearyl A 2.2 1 1.5 2 3 2 sulfate* (emulsifier) Myrj 59* A 2 2 2 2 2 1(emulsifier) Span 60* A 2 2 2 2 2 1 (emulsifiers) Di-thiane B 0.05 0.052.0 2.0 3.5 3.5 5.0 10.0 Resorcinol Micronized Zinc B 2.50 5.00 5.002.50 2.50 5.00 2.50 5.00 Oxide KOH, 22% (form in 2.20 situ soap withstearic acid) Octyl 2.50 2.50 2.50 2.50 methoxycinnamate Water B BAL BALBAL BAL BAL BAL BAL Glycerin B 1 1 1 1 1 1 1 1

EXAMPLE 12 Mushroom Tyrosinase Assay

Mushroom tyrosinase inhibition is indicative of reduction in melaninsynthesis, thereby showing skin lightening effect. This experiment showsthe efficacy of resorcinol derivatives of the present invention.

Into each well of a 96-well plate, 150 microliters of phosphate buffer(100 mM, pH 7.0), 10 microliters of L-DOPA(L-3,4-Dihydroxyphenylalanine, 10 mM), and 20 microliters of skinlightening agent (dissolved in ethanol, which is the control) wereadded. Following an initial measurement of background absorbency at475-nm, 20 microliters of mushroom tyrosinase (Sigma T-7755; 6050units/ml) was added and incubated at room temperature.

Absorbency is read at 475-nm over the following time points: 0, 2, 4,and 6.5 minutes. The data is plotted as 475-nm absorbency vs. time(minutes) and the slope of the line is calculated (ΔAbs 475nm/min).Values are expressed as the percentage of the respective untreatedethanol control reaction.${\%\quad{of}\quad{Control}} = {\frac{( {{Reaction}\quad{rate}\quad{for}\quad{treated}\quad{reaction}} )}{( {{Reaction}\quad{rate}\quad{for}\quad{untreated}\quad{control}} )} \times 100\%}$

TABLE 8 Mushroom Tyrosinase Assay Results % of Control CompoundConcentration (Melanin Synthesis) 4-Ethyl Resorcinol  0.1 uM 73   1 uM46   10 uM 31  100 uM 21 1,3-di-Thiane  0.1 uM 87 Resorcinol   1 uM 57  10 uM 48  100 uM 47 Resorcinol  0.1 uM 97   1 uM 98   10 uM 98  100 uM100 

The data show that the inventive compounds are substantially aseffective or slightly less effective than 4-ethyl resorcinol, bothcompounds having good skin lightening effects. An advantage of theinventive compounds is that they are relatively easy and cost-effectiveto manufacture. Resorcinol, which has only a single hydrogen at the4-position, does not display activity in the above assay and does notyield a skin lightening benefit.

It should be understood that the specific forms of the invention hereinillustrated and described are intended to be representative only.Changes, including but not limited to those suggested in thisspecification, may be made in the illustrated embodiments withoutdeparting from the clear teachings of the disclosure. Accordingly,reference should be made to the following appended claims in determiningthe full scope of the invention.

1. A cosmetic method of skin lightening comprising applying to the skina composition comprising: a. about 0.000001 to about 50% of a compoundof general formula I

Wherein X=Carbon, Nitrogen, Sulfur or Oxygen; each A₁ and/or A₂independently is =H, COR, CO₂R, CONHR where R=C₁-C₁₈ saturated orunsaturated hydrocarbon; and each Y₁ and/or Y₂ independently is H,C₁-C₁₈ saturated or unsaturated hydrocarbon, or OZ, where Z=H, COR¹,CO₂R¹, CONHR¹ and where R¹=C₁-C₁₈ saturated or unsaturated hydrocarbon;and b. a cosmetically acceptable carrier.
 2. The method of claim 1,wherein said compound of general formula I is esterified with an acidselected from the group consisting of ferulic acid, vanillic acid,sebacic acid, azaleic acid, benzoic acid, caffeic acid, coumaric acid,salicylic acid, cysteine, cystine, lactic acid, glycolic acid andmixtures thereof.
 3. The method of claim 1, wherein said compositionfurther comprises a sunscreen.
 4. The method of claim 3, wherein saidsunscreen is a micronized metal oxide.
 5. The method of claim 1, whereinsaid compound is a compound of formula II:

wherein X=Carbon, Nitrogen, Sulfur or Oxygen.
 6. The method of claim 1,wherein said composition further comprises a fragrance.
 7. The cosmeticmethod according to claim 1, wherein said composition further comprisesa skin benefit agent selected from the group consisting of alpha-hydroxyacids, beta-hydroxy acids, polyhydroxy acids, hydroquinone, t-butylhydroquinone, niacinamide, Vitamin C derivatives, dioic acids, linoleicacid, retinoids, resorcinol derivatives, and mixtures thereof.
 8. Thecosmetic method of claim 1, wherein said composition further comprisesan organic sunscreen selected from the group consisting ofBenzophenone-3, Benzophenone-4, Benzophenone-8, DEA, Methoxycinnamate,Ethyl dihydroxypropyl-PABA, Glyceryl PABA, Homosalate, Methylanthranilate, Octocrylene, Octyl dimethyl PABA, Octyl methoxycinnamate(PARSOL MCX), Octyl salicylate, PABA, 2-Phenylbenzimidazole-5-sulphonicacid, TEA salicylate, 3-(4-methylbenzylidene)-camphor, Benzophenone-1,Benzophenone-2, Benzophenone-6, Benzophenone-12, 4-Isopropyl dibenzoylmethane, Butyl methoxy dibenzoyl methane (PARSOL 1789),Etocrylene, andmixtures thereof.
 9. A cosmetic composition comprising: a. about0.000001 to about 50% of a compound of general formula I

Wherein X=Carbon, Nitrogen, Sulfur or Oxygen; each A₁ and/or A₂independently is =H, COR, CO₂R, CONHR where R=C₁-C₁₈ saturated orunsaturated hydrocarbon; and each Y₁ and/or Y₂ independently is H,C₁-C₁₈ saturated or unsaturated hydrocarbon, or OZ, where Z=H, COR¹,CO₂R¹, CONHR¹ and where R¹=C₁-C₁₈ saturated or unsaturated hydrocarbon;and b. a cosmetically acceptable carrier.
 10. The cosmetic compositionof claim 9, wherein said compound is a compound of general formula II:

wherein X=Carbon, Nitrogen, Sulfur or Oxygen.
 11. The cosmeticcomposition of claim 9, wherein said compound comprises about 0.00001%to about 10% of said composition.
 12. The cosmetic composition of claim9, wherein said compound comprises about 0.001% to about 7% of saidcomposition.
 13. The cosmetic composition of claim 9, wherein saidcompound comprises about 0.01% to about 5% of said composition.
 14. Thecosmetic composition of claim 9, further comprising a sunscreen.
 15. Thecosmetic composition of claim 14, wherein said sunscreen is a micronizedmetal oxide.
 16. The cosmetic composition of claim 10, wherein thehydroxy groups of said compound of general formula II are esterifiedwith an acid selected from the group consisting of ferulic acid,vanillic acid, sebacic acid, azaleic acid, benzoic acid, caffeic acid,coumaric acid, salicylic acid, cysteine, cystine, lactic acid, glycolicacid and mixtures thereof.